Announcement Type
This is a reissue of RFA-CA-07-001,
which was previously released December 8, 2005, and now is divided into
separate Funding Opportunity Announcements (FOAs) for R33 and R21grant
mechanisms.

Update: The following update relating to this announcement has been issued:

NOTICE: Applications
submitted in response to this FOA for Federal assistance must be submitted
electronically through Grants.gov (http://www.grants.gov)
using the SF424 Research and Related (R&R) forms and SF424 (R&R)
Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER
FORMAT.

This FOA must be read in conjunction with the application
guidelines provided with this announcement in Grants.gov/Apply for Grants (hereafter
called Grants.gov/Apply).

A registration process is necessary before submission and
applicants are highly encouraged to start the process at least 4 weeks prior to
the grant submission date. See Section
IV.

This
Funding Opportunity Announcement (FOA) issued by the National Cancer Institute
(NCI), National Institutes of Health (NIH), solicits exploratory grant
applications for research projects proposing the development of highly
innovative cancer-relevant molecular biology technologies. Technology
encompasses methods and tools that enable research, including, but not limited
to, instrumentation, techniques, and devices.

This FOA will
utilize the NIH Exploratory/Developmental
Phase II Grant (R33) award mechanism and runs in
parallel with another FOA of identical scientific scope, RFA-CA-07-015,
that invites applications under the Exploratory/Developmental Grant (R21) award
mechanism.

This
funding opportunity is part of a broader NCI-sponsored Innovative
Molecular Analysis Technologies (IMAT) Program. Several IMAT FOAs of
identical or closely related scientific scope using various funding
mechanisms are available. To facilitate selection, a separate NIH Guide Notice
provides brief cross-comparison and links to all the IMAT FOAs (NOT-CA-06-025).

Awards
issued under this FOA are contingent upon the availability of funds and
the submission of a sufficient number of meritorious applications.

The NCI intends to commit a total of up to
$1,500,000 to this FOA in fiscal year 2007 to fund up to 4-5 grants.

Because
the nature and scope of the proposed research will vary from application
to application, it is anticipated that the size and duration of each award
will also vary. The total amount awarded and the number of awards will
depend upon the mechanism numbers, quality, duration, and costs of the applications
received.

Budget and Project Period: An applicant for an R33 grant may
request a project period of up to 3 years with a budget appropriate for
the science proposed.

Eligible
Organizations: For-profit
organizations; non-profit organizations; public or private institutions,
such as universities, colleges, hospitals, and laboratories; units of
State governments; units of local governments; eligible agencies of the
Federal government; domestic institutions; foreign institutions; faith-based
or community-based organizations; Indian/Native American Tribal Government (Federally Recognized);
Indian/Native American Tribal Government (Other than Federally
Recognized); and Indian/Native American Tribally Designated Organization.

Eligible Project Directors/Principal
Investigators (PDs/PIs): Any individual with the skills, knowledge, and
resources necessary to carry out the proposed research is invited to work
with their institution to develop an application for support. Individuals
from underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH support.

Applicants may submit more than one application,
provided each application is scientifically distinct.

Once funded as a PD/PI via this
FOA, an individual is then ineligible to submit another application as a
PD/PI for this FOA.

See Section
IV.1 for application materials. The
SF424 (R&R) Application Guide for this FOA is located at these web
sites:

This Funding
Opportunity Announcement (FOA) issued by the National Cancer Institute (NCI), National Institutes of
Health (NIH), solicits
applications for research projects proposing the
development of highly innovative cancer-relevant molecular analysis technologies.
Technology encompasses methods and tools that enable research, including, but
not limited to, instrumentation, techniques, and devices. Technology is
distinct from resources such as databases, reagents, and tissue repositories. Applications for support of such resources will not be considered responsive to
this funding opportunity announcement. Technologies solicited include, but are
not necessarily limited to, those that are suitable for the detection of
alterations and instabilities of genomic DNA; measurement of the expression of
genes and gene products, including proteins; analysis and detection of gene
and/or cellular products, including post-translational modification and
function of proteins; identification and characterization of exogenous infectious
agents in cancer; and assaying the function of major signal transduction
networks involved in cancer. Developing technologies would include those that
will support molecular analyses in vitro, in situ, and/or in
vivo in discovery processes as well as in pre-clinical models and clinical
research.

This
funding opportunity is part of a broader NCI-sponsored Innovative Molecular
Analysis Technologies (IMAT) Program. The IMAT program underscores the desire
of NCI to develop and integrate novel technologies focused on the molecular
analysis of cancers and their micro-environments in support of cancer research,
diagnosis, and treatment. In the research continuum of discovery, development,
and delivery, this program emphasizes the link between development and
delivery. This specific initiative will serve as a tool to develop emerging
technologies in an appropriate biological or clinical context.

The
continuation of the IMAT Program consists of the following three related
themes:

Innovative Technologies for the Molecular Analysis of
Cancer, which
emphasizes research projects centered on inception and early stage
development of new technologies for cancer research;

Application of Emerging Technologies for Cancer
Research, which
is designed to support research projects evaluating technologies that are
ready for initial clinical or laboratory application in cancer research;
and

Innovations in Cancer Sample Preparation, which is centered on the development of novel sample preparation technologies suitable
for the molecular analysis of cancer cells and their host environment.

For
each IMAT theme, parallel FOAs exist that utilize various funding mechanisms,
such as R21, R33, R21/R33, and the Small Business Innovation Research (SBIR)
and Small Business Technology Transfer (STTR) grant mechanisms (R41, R42,
R41/R42, R43, R44, R43/R44) intended for applicants from small business (SB)
concerns. The overall goal of the IMAT program is to accelerate meritorious
technology development projects by minimizing the funding gap between
feasibility and development phases. Through the use of appropriate funding
mechanisms, the individual IMAT FOAs are focused either on: (1) the Phase I or
high-risk exploratory portion of an investigator's scientific effort, with an
emphasis on innovation; or (2) the developmental Phase II projects; or (3)
combined phased innovation mechanism (Fast-Track for SBIR/STTR). Whereas the
scientific scopes within the main IMAT themes remain constant, FOAs with the
focus on exploratory pilot phases and on developmental phases have distinct
submission requirements.

The
complete matrix of multiple IMAT FOAs, including their scopes and basic
requirements, is outlined in a separate notice NOT-CA-06-025.
Potential applicants interested in IMAT initiatives are strongly advised to use
that NIH Guide Notice as a “switchboard” to verify which of the closely
related active FOAs might be most appropriate for them to apply to.

Note: Researchers who emphasize the assessment of in vivo imaging
technologies as the primary focus of their grant applications should contact
the Cancer Imaging Program for
information on appropriate funding opportunities. Researchers focusing on
applying new bioinformatics or statistical techniques as the primary focus of
their applications should consider one of the Biomedical Information
Science and Technology Initiative (BISTI) opportunities.

Background

In
order to reduce death and suffering due to cancer, the NCI will continue to
support the development of creative methods to understand, prevent, diagnose,
and treat cancer. In the past several decades, basic discovery research has
revealed that cancer is a complex disease involving myriad molecular and
cellular processes, and that cancers arise as the result of the gradual
accumulation of genetic changes in specific cells. Identifying which subset of
the genes encoded within the human genome can contribute to the development of
cancer remains a challenge. Even more challenging is the subsequent
understanding of the roles of RNA, proteins, and other functional products
encoded by these genes. The identification and characterization of these cancer
genes and their associated gene products remains a high priority in cancer
research. New technologies and approaches not only address specific questions
in basic research and clinical practice, but are also beneficial in uncovering
and developing new directions and paradigms in cancer research. Therefore,
technological advances play critical roles throughout the NCI's mission.

The
IMAT program was originally designed in 1999 with three objectives, which were
(and continue to be): to focus technology development on cancer; to solicit
highly innovative technology development projects; and to accelerate the rate
of maturation of meritorious technologies from feasibility through development
of the technology. Through solicitation, outreach, and communication with the
investigator community, the IMAT Program has been successful in promoting
cancer-relevant applications of a diverse spectrum of new and emerging
technologies. The program has focused on both the inception and development of
cancer-related technologies. Some of the technologies originally generated with
IMAT funding have been put in use to facilitate the acquisition of basic
knowledge about cancer, which feeds the discovery pipeline. Other
IMAT-supported technologies have been applied to questions of clinical
importance.

This
FOA is intended to support the development of molecular analysis tools that
will not only allow for the more in depth examination of the molecular basis of
cancer in general, but will also provide the ability to identify those
molecular characteristics of individuals that are pertinent to cancer
development and prognosis. For instance, such tools are anticipated to
facilitate the identification of genetic factors that influence an individual's
risk of developing cancer or his/her ability to respond to adverse
external/environmental factors such as radiation, carcinogens, as well as to
therapeutic agents.

To
better understand the neoplastic process and the molecular responses of the
host to cancer, it will be critical not only to acquire relevant knowledge at
the DNA level, but also to improve our understanding of the impact of aberrant
genetic information on cellular functions. Current discoveries indicate that
alterations in many of the cellular processes, pathways, and/or networks may
contribute to the genesis of cancer and that these alterations could be
exploited for therapeutic or preventive intervention. Therefore, it is
important to invoke technologies that can detect molecular changes in the cell
without preconceived ideas as to what specific markers might be the most
valuable to monitor. In the discovery phase, the emphasis will be on highly
multiplexed technologies that can effectively detect structural variations or
functional changes in many (ultimately in all) members of the populations of
DNA, RNA, or protein species present in cells. Current technologies for the
multiplexed analysis of macromolecular species are at a stage where the
greatest utility exists for the analysis of large numbers of relatively
homogeneous cell populations that can be assayed in vitro. While many of the
existing technologies have relatively sophisticated multiplexing capabilities
in the assay format, none are comprehensive for any particular type of
macromolecular species (DNA, RNA, or protein). Therefore, there is a need for
further development to insure that the resulting technologies provide enhanced
assay potential, adequate sensitivity and specificity, robust data analysis
tools, and easy adaptation to the basic, preclinical, and clinical research
settings.

Objectives and Scope

The
purpose of this FOA is to solicit applications from individuals and groups
interested in developing novel technologies suitable for the molecular analysis
of cancers and their host environment in support of basic, clinical, and
epidemiological research. Technologies to support research in the following
areas are considered to be appropriate. Examples given below are not intended
to be all-inclusive, but serve to illustrate the types of capabilities that are
of interest.

New
tools that would allow for acquisition of more complete profiles of DNA, RNA,
protein, and other important biomolecules of normal, pre-cancerous, and
cancerous cells are needed to support the basic discovery process by offering a
more complete picture of the neoplastic phenomenon. Analogous technological
advances will also be needed to examine the tumor micro-environment, including
both stromal and vascular interactions. Such tools will allow more
comprehensive characterization of both the variations that influence
predisposition to cancer and the responses of an individual to therapeutic and
preventive agents. The types of capabilities, technologies, and data analysis
tools that are of interest include, but are not limited to, the following
examples:

Scanning for and identification of the sites of chromosomal
aberrations, mutations, and polymorphisms that reflect inherited
abnormalities as well as somatic alterations associated with aging and/or
resulting from exposure to environmental mutagenic factors, such as
oxidative stress, ionizing or ultraviolet radiation, and carcinogens
(particular interest is in the development of scalable tools that can be
applied across whole genomes, for example, to detect rare abnormalities in
mixed populations of normal and abnormal cells);

Technologies for detection and characterization of
foreign nucleic acid sequences, such as DNA of as yet uncharacterized
exogenous infectious agents, that might be present in human cancer cells;

Massively parallel analysis of the expression of genes
that would overcome limitations of the existing multiplexed gene
expression technologies;

Detection
of expression of proteins and their posttranslational modifications,
including technologies suitable for expansion to profiling of all proteins
expressed in cells, detecting rare protein variants in mixed populations,
and detecting proteins modified (adducted) by carcinogens or anticancer
drugs;

Monitoring the function of specific proteins and
cellular metabolic or signaling pathways, including such aspects as
examination of ligand-protein and protein-protein complexes and
technologies for simultaneous monitoring of functions of all members of a
class of proteins or a complete metabolic or signaling pathway;

For
all technologies proposed for development, it is important to substantiate the
potential value of and role for the technology in elucidating the molecular
characteristics of cancer cells or cancer-relevant characteristics of the
individual. It is also important for applicants to discuss the prospects for
the eventual dissemination of new technologies to other laboratories or the
clinic. In the case of technologies intended for use on clinical specimens or
in patients, collaborations with investigators involved in the clinical
research of cancer are encouraged.

Exploratory/developmental grant support is for new
projects only; competing renewal (formerly “competing continuation”)
applications will not be accepted. Up to two resubmissions (formerly
“revisions/amendments") of a previously reviewed exploratory/developmental
grant application may be submitted. See NOT-OD-03-041,
May 7, 2003.

2.
Funds Available

Because the nature and scope of the proposed research will
vary from application to application, it is anticipated that the size and
duration of each award will also vary. Although the financial plans of the NCI
provide support for this program, awards pursuant to this funding opportunity
are contingent upon the availability of funds and the submission of a sufficient
number of meritorious applications.

The NCI intends to
commit a total of approximately up to $1,500,000 to this FOA in FY 2007 to
award up to 4-5 grants in response to this FOA.

An R33 applicant may request a project period of up to 3
years with a combined budget appropriate for the science proposed. The request should be tailored to the needs of the
project. Commensurate
Facilities and Administrative (F&A) costs are allowed. NIH grants policies as described
in the NOT-OD-05-004,
November 2, 2004.

All awards are subject to the availability of funds. The estimated amount of funds available for support of
projects awarded as a result of this announcement is up to $1,500,000 for
fiscal year 2007. Future year

amounts will depend on annual appropriations.

Section
III. Eligibility Information

1. Eligible Applicants

1.A. Eligible InstitutionsYou may submit an
application(s) if your organization has any of the following characteristics:

For-profit organizations

Non-profit organizations

Public or private institutions,
such as universities, colleges, hospitals, and laboratories

Units of State governments

Units of local governments

Eligible agencies of the Federal
government

Domestic institutions/organizations

Foreign institutions/organizations

Faith-based or community-based
organizations

Indian/Native
American Tribal Government (Federally Recognized)

Indian/Native
American Tribal Government (Other than Federally Recognized)

Indian/Native
American Tribally Designated Organization

1. B.
Eligible Individuals

Any
individual with the skills, knowledge, and resources necessary to carry out the
proposed research as the Project Director/Principal Investigator (PD/PI) is
invited to work with his/her institution to develop an application for support.
Individuals from underrepresented racial and ethnic groups as well as
individuals with disabilities are always encouraged to apply for NIH support.

To download a SF424 (R&R) Application Package and SF424
(R&R) Application Guide for completing the SF424 (R&R) forms for this
FOA, link to http://www.grants.gov/Apply/ and follow
the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

The individual designated as the
PD/PI on the application must also be registered in the NIH eRA Commons.
It is not necessary for PDs/PIs to register with Grants.gov.

The PD/PI must hold a PD/PI
account in the Commons and must be affiliated with the applicant
organization. This account cannot have any other role attached to it other
than the PD/PI.

This registration/affiliation must
be done by the Authorized Organization Representative/Signing Official (AOR/SO)
or their designee who is already registered in the Commons.

Both the PD/PI and AOR/SO need
separate accounts in the NIH eRA Commons since both are authorized to view
the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an
Individual DUNS and CCR registration, that particular DUNS number and CCR
registration are for the individual reviewer only. Those registrations are
different than any DUNS number and CCR registration used by an applicant
organization. Individual DUNS and CCR registrations should be used only for the
purposes of personal reimbursement and should not be used on any grant
applications submitted to the Federal Government.

Several of the steps of the registration process could
take 4 weeks or more. Therefore, applicants should immediately check with their
business official to determine whether their institution is already registered
in both Grants.gov and the Commons. The NIH will accept
electronic applications only from organizations that have completed all
necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R &R) application forms and SF424
(R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used.
Applicants will not be able to use any other SF424 (R&R) forms (e.g.,
sample forms, forms from another FOA), although some of the “Attachment” files
may be useable for more than one FOA.

Prepare all applications using the SF424 (R&R)
application forms and the SF424 (R&R) Application Guide (MS
Word or PDF).

The SF424 (R&R) Application Guide is critical to
submitting a complete and accurate application to NIH.

There are fields within the SF424 (R&R) application
components that, although not marked as mandatory, are required by NIH (e.g.,
the “Credential” log-in field of the “Research & Related Senior/Key Person
Profile” component must contain the PD/PI’s assigned eRA Commons User ID).
Agency-specific instructions for such fields are clearly identified in the
Application Guide. For additional information, see “Tips and Tools for Navigating
Electronic Submission” on the front page of “Electronic Submission of Grant
Applications.”

The SF424 (R&R) application is comprised of data
arranged in separate components. Some components are required, others are
optional. The forms package associated with this FOA in Grants.gov/APPLY will include all
applicable components, required and optional. A completed application in
response to this FOA will include the following components:

Proposed research should provide special opportunities for furthering
research programs through the use of unusual talent, resources, populations, or
environmental conditions in other countries that are not readily available in
the United States or that augment existing U.S. resources.

Prospective applicants are asked to submit a letter of
intent that includes the following information:

Descriptive title of proposed
research.

Name, address, and telephone
number of the PD/PI.

Names of other key personnel.

Participating institutions.

Number and title of this funding
opportunity.

Although a letter of intent is not required, is not
binding, and does not enter into the review of a subsequent application, the
information that it contains allows NIH staff to estimate the potential review
workload and plan the review.

The letter of intent is to be sent by the date listed at
the beginning of this document.

To submit an application
in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow
steps 1-4. Note: Applications must only be submitted electronically.PAPER APPLICATIONS
WILL NOT BE ACCEPTED.

3.C.
Application Processing

Applications may be submitted on or after the
opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the
applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by
the receipt date(s) and time, the application may be delayed in the review
process or not reviewed.

Once an application
package has been successfully submitted through Grants.gov, any errors have
been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have
two business days to view the application image.

If
everything is acceptable, no further action is necessary. The application will
automatically move forward for processing by the Division of Receipt and
Referral, Center for Scientific Review, NIH, after two business days.

Prior
to the submission deadline, the AOR/SO can “Reject” the assembled application
and submit a changed/corrected application within the two day viewing window.
This option should be used if the AOR/SO determines that warnings should be
addressed. Reminder: warnings do not stop further application processing. If an
application submission results in warnings (but no errors) it will
automatically move forward after two business days if no action is taken.
Please remember that some warnings may not be applicable or may need to be
addressed after application submission.

If
the two day window falls after the submission deadline, the AOR/SO will have
the option to “Reject” the application if, due to an eRA Commons or Grants.gov
system issue, the application does not correctly reflect the submitted
application package (e.g., some part of the application was lost or didn’t
transfer correctly during the submission process). The AOR/SO should first contact
the eRA
Commons Helpdesk to confirm the system error, document the issue,
and determine the best course of action. NIH will not penalize the applicant
for an eRA Commons or Grants.gov system issue.

If
the AOR/SO chooses to “Reject” the image after the submission deadline for a
reason other than an eRA Commons or Grants.gov system failure, a
changed/corrected application still can be submitted but it will be subject to
the NIH late policy guidelines and may not be
accepted. The reason for this delay should be explained in the cover letter
attachment.

Both
the AOR/SO and PD/PI will receive e-mail notifications when the application is
rejected or the application automatically moves forward in the process after
two days.

Upon receipt,
applications will be evaluated for completeness by the Center for Scientific
Review, NIH. Incomplete applications will not be reviewed.

There will be an
acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the
assignment of an application to a Scientific Review Group is also in the Commons.

The
NIH will not accept any application in response to this FOA that is essentially
the same as one currently pending initial merit review unless the applicant
withdraws the pending application. The NIH will not accept any application that
is essentially the same as one already reviewed. This does not preclude the
submission of an application already reviewed with substantial changes, but
such application must include an “Introduction” addressing the previous
critique. Note such an application is considered a "resubmission" for
the SF424 (R&R).

All
NIH awards are subject to the terms and conditions, cost principles, and other
considerations described in the NIH Grants
Policy Statement.

Pre-Award
Costs are allowable. A grantee may, at its own risk and without NIH prior
approval, incur obligations and expenditures to cover costs up to 90 days
before the beginning date of the initial budget period of a new award if such
costs: are necessary to conduct the project and would be allowable under the
grant, if awarded, without NIH prior approval. If specific expenditures would
otherwise require prior approval, the grantee must obtain NIH approval before
incurring the cost. NIH prior approval is required for any costs to be incurred
more than 90 days before the beginning date of the initial budget period of a
new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement.

6. Other Submission Requirements

The NIH requires the PD/PI to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Tips and Tools for Navigating Electronic Submission” on the front page of “Electronic Submission of Grant Applications.”

All application instructions outlined in the SF424
(R&R) Application Guide are to be followed, with the following requirements
for R33 applications:

R33 applications will use the non-modular
budget format and "Just-in-Time" concept.

Preliminary data are required for
an R33 application and must be included.

Items 2-5 of the Research Plan component
of the R33 application may not exceed 25 pages, including tables, graphs,
figures, diagrams, and charts.

“Introduction” (required for a
resubmission application) is limited to three pages.

R33 appendix materials should be
limited, as is consistent with the developmental nature of the R33
mechanism. The following materials may be included in the appendix:

Up to five publications,
manuscripts (accepted for publication), abstracts, patents, or
other printed materials directly relevant to this project. Do not
include manuscripts submitted for publication.

Publications in press:
Include only a publication list with a link to the publicly available on-line
journal article or the NIH PubMed Central (PMC) submission identification
number. Do not include the entire article.

Manuscripts accepted for
publication but not yet published: The entire article may be
submitted electronically as a PDF attachment.

Manuscripts published but a
publicly available online journal link is not available: The
entire article may be submitted electronically as a PDF attachment.

Graphic images of gels,
micrographs, etc. provided that the image (may be reduced in size) is also
included within the 25-page limit of Items 2-5 of the Research Plan.
No images may be included in the Appendix that are not also represented within
the Research Plan.

Do not use the Appendix to
circumvent the page limitations of the Research Plan. An application that
does not observe these limitations may be delayed in the review process.

Note: While each section of the Research Plan needs to be
uploaded separately as a PDF attachment, applicants are encouraged to construct
the Research Plan as a single document, separating sections into distinct PDF
attachments just before uploading the files. This approach will enable
applicants to better monitor formatting requirements such as page limits. All
attachments must be provided to NIH in PDF format, filenames must be included
with no spaces or special characters, and a .pdf extension must be
used.

Other Specific Instructions
for Preparation of an R33 Application

R33 applicants must present detailed preliminary data in
support of the feasibility of the proposed technology or approach that is
proposed for development. These applications will also have the added burden of
demonstrating the innovation of the particular technology or approach. Please
note that there is a strict 25-page limit for R33 applications.

For R33 applicants applying to continue research begun
under R21 support, the applicant must quote the final milestones from the R21
Notice of Award as part of the R33 application. This section should
include a discussion of the extent to which the applicant achieved the
milestones. This section should constitute no more than three pages, but
is in addition to the 25-page limit.

Research Plan:

Preliminary Studies/Progress Report

This section must document that feasibility studies have
been completed, and progress achieved, equivalent to that expected through the
support of an R21 project. The applicant must clearly describe how the exploratory/developmental
study is ready to be scaled up to an expanded application stage. In the event
that an applicant feels that the technology is too proprietary to disclose, the
applicant must at a minimum provide a demonstration (results) of the capabilities
of the proposed technology. Preliminary data relevant to both the technology
evaluations and the pilot biological study should be presented.

R33 applications should also include milestones as
described in the section above that may help justify continued support under
another mechanism, such as a Research Project Grant (R01) application.

Other Budgetary Requirements. An annual meeting of all
investigators funded through this program will be held to share progress and
research insights that may lead to further progress in the program. Applicants
should request travel funds in their budgets for the PD/PI and one additional
senior investigator to attend this annual meeting.

Intellectual Property Management Plan

Certain research plans will require collaboration and
coordination between investigators at different institutions, some of whom may
not be NIH funding recipients and who may have pre-existing intellectual
property obligations to third parties. It is anticipated that commercial
embodiments of the results of such research may incorporate single inventions
shared by several institutions, or multiple inventions each from a separate
institution. Therefore, prior to funding, R33 grant applicants must address how
they will coordinate patent prosecution and licensing activities, if necessary
to enable a licensee to access the bundle of intellectual property needed to
take a product to market on commercially viable terms. Suggested strategies
include: (1) assigning intellectual property rights to related inventions to an
invention management firm; (2) designating one organization to take the lead on
patenting and licensing related inventions; and (3) agreeing in advance that if
multiple parties are to independently license-related inventions, the total of
stacked royalties will not exceed a predetermined percentage rate.

The technology transfer/ intellectual property
management/licensing officer or equivalent of the PI's institution is to submit
an intellectual property management plan, including at least those elements
above. Alternatives to the suggested strategies, which accomplish the same
goals, will be considered. Intellectual property management plans are a
just-in-time requirement and do not need to be included in the grant
application but plans will be required before an R33 grant can be awarded.

The applicant's institution should avoid exclusively
licensing those inventions that are research tools unless either: (1) the field
of use of the exclusive license is restricted to commercial use; or (2) the exclusive
licensee will make the research tool available on reasonable terms. Applicants
are directed to the NIH policy on the dissemination of biological research
resources (“research tools”) at http://www.ott.nih.gov/policy/rt_guide_final.html.

Plan
for Sharing Research Data

All
applicants must describe their plans for disseminating information about, and
providing access to the technology developed under this grant support.
For example, the technology might be made available as a fee-for-service,
through sale of instruments and/or reagents, through collaboration, through
publication and posting of results, plans and methods, or by other means.

Applicants
should include a brief one paragraph description of how final research data
will be shared, or explain why data-sharing is not possible. The specific
nature of the data to be collected will determine whether or not the final
dataset may be shared. If the final data are not amenable to sharing, for
example, if they are proprietary, this must be explained in the application.

Applicants are encouraged to discuss their data-sharing
plan with the NCI staff likely to accept assignment of their application.

The
precise content of the data-sharing plan will vary, depending on the data being
collected and how the investigator is planning to share the data. Applicants
who are planning to share data may wish to describe briefly the expected
schedule for data sharing, the format of the final dataset, the documentation
to be provided, whether or not any analytic tools also will be provided,
whether or not a data-sharing agreement will be required and, if so, a brief
description of such an agreement (including the criteria for deciding who can
receive the data and whether or not any conditions will be placed on their
use), and the mode of data sharing (e.g., under their own auspices by mailing a
disk or posting data on their institutional or personal website, through a data
archive or enclave). Investigators choosing to share under their own auspices
may wish to enter into a data-sharing agreement. References to data sharing may
also be appropriate in other sections of the application.

All applicants must
include a plan for sharing research data in their application. All
investigators responding to this funding opportunity should include a
description of how final research data will be shared, or explain why data
sharing is not possible.

NIH policy
requires that grant awardee recipients make unique research resources readily
available for research purposes to qualified individuals within the scientific
community after publication (see the NIH Grants Policy Statement at https://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a plan for
sharing research resources addressing how unique research resources will be
shared or explain why sharing is not possible.

The
adequacy of the resources sharing plan and any related data sharing plans will
be considered by NIH/NCI program staff when making recommendations about
funding applications. The effectiveness of the resource sharing will be
evaluated as part of the administrative review of each Non-Competing Grant
Progress Report (PHS 2590). See Section VI.3.,
“Reporting.”

Section V. Application Review Information

1.
Criteria

Only the review
criteria described below will be considered in the review process.

2. Review and Selection Process

Applications
submitted for this funding opportunity will be assigned to the NIH Institutes
and Centers (ICs) on the basis of established Public Health Service (PHS)
referral guidelines.

Applications that are complete and responsive to the FOA
will be evaluated for scientific and technical merit by an appropriate peer
review group convened by the NCI in accordance with the review criteria stated below.

As
part of the initial merit review, all applications will:

Undergo a
selection process in which only those applications deemed to have the highest
scientific merit, generally the top half of applications under review, will be
discussed and assigned a priority score;

Receive a written
critique; and

Receive a second
level of review by the National Cancer Advisory Board.

Applications
submitted in response to this funding opportunity will compete for available
funds with all other recommended R33 applications. The following will be
considered in making funding decisions:

Scientific merit
of the proposed project as determined by peer review.

Availability of
funds.

Relevance to
program priorities.

The
goals of NIH supported research are to advance our understanding of biological
systems, to improve the control of disease, and to enhance health. In their
written critiques, reviewers will be asked to comment on each of the following
criteria in order to judge the likelihood that the proposed research will have
a substantial impact on the pursuit of these goals. Each of these criteria will
be addressed and considered in assigning the overall score, weighting them as
appropriate for each application.

Significance

Approach

Innovation

Investigator

Environment

Additional Review Criteria

Note
that an application does not need to be strong in all categories to be judged
likely to have major scientific impact and thus deserve a high priority score.
For example, an investigator may propose to carry out important work that by
its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an
important scientific health problem? If the aims of the application are
achieved, how will scientific knowledge or clinical practice be advanced? What
will be the effect of these studies on the concepts, methods, technologies,
treatments, services, or preventative interventions that drive this field?To what degree does the proposed
research support the needs of the IMAT program?

Approach: Are the conceptual or
clinical framework, design, methods, and analyses adequately developed, well
integrated, well reasoned, and appropriate to the aims of the project? Does the
applicant acknowledge potential problem areas and consider alternative tactics? What is the time frame for developing the proposed approaches, tools or
technology applications/implementations?

Innovation: Is the project original and innovative? For example:
Does the project challenge existing paradigms or clinical practice; address an
innovative hypothesis or critical barrier to progress in the field? Does the
project develop or employ novel concepts, approaches, methodologies, tools, or
technologies for this area?

Investigators: Are the investigators appropriately trained and well
suited to carry out this work? Is the work proposed appropriate to the
experience level of the PD/PI and other researchers? Does the investigative
team bring complementary and integrated expertise to the project (if
applicable)?

Environment: Does the scientific
environment in which the work will be done contribute to the probability of success?
Do the proposed studies benefit from unique features of the scientific
environment, or subject populations, or employ useful collaborative
arrangements? Is there evidence of institutional support?

2.A.
Additional Review Criteria:

In
addition to the above criteria, the following items will be considered in the
determination of scientific merit and the priority score:

Feasibility: R33 applicants must
present detailed preliminary data in support of the feasibility of the proposed
technology or approach that is proposed for development. They will also have
the added burden of demonstrating the innovation of the particular technology
or approach. Feasibility means that some preliminary experiments have been
performed and that sufficient technical data exist to support proof of
principle of the technology/hypothesis and provide a solid
foundation for the proposed Phase II activity. For R33
applications to continue research begun under R21 support, the reviewers will
assess whether or not the final milestones from the R21 Notice of Award have
been accomplished.

Protection of Human Subjects from Research Risk: The involvement of human
subjects and protections from research risk relating to their participation in
the proposed research will be assessed. See item 6 of the Research Plan
component of the SF424 (R&R).

Inclusion
of Women, Minorities and Children in Research: The adequacy of plans to
include subjects from both genders, all racial and ethnic groups (and
subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of subjects
will also be evaluated. See item 7 of the Research Plan component of the SF424
(R&R).

Care and Use of Vertebrate Animals in
Research: If vertebrate animals are to
be used in the project, the five items described under item 11 of the Research
Plan component of the SF424 (R&R) will be assessed.

Biohazards: If materials or procedures are proposed that are
potentially hazardous to research personnel and/or the environment, determine
if the proposed protection is adequate.

2.B. Additional
Review Considerations

Budget and Period of
Support: The
reasonableness of the proposed budget and the appropriateness of the requested
period of support in relation to the proposed research may be assessed by the
reviewers. Is the percent effort listed for the PD/PI appropriate for the work
proposed? Is each budget category realistic and justified in terms of the aims
and methods?

NIH policy requires that grant awardee recipients make
unique research resources readily available for research purposes to qualified
individuals within the scientific community after publication (see the NIH Grants Policy Statementhttps://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a plan for sharing
research resources addressing how unique research resources will be shared or
explain why sharing is not possible.

NCI
program staff will be responsible for the administrative review of the plan for
sharing research resources.

The
adequacy of the resources sharing plan and any related data sharing plans will
be considered by NCI program staff when making recommendations about funding
applications. Program staff may negotiate modifications of the data and
resource sharing plans with the awardee before recommending funding of an
application. The final version of the data and resource sharing plans
negotiated by both will become a condition of the award of the grant. The
effectiveness of the resource sharing will be evaluated as part of the
administrative review of each Non-Competing Grant
Progress Report (PHS 2590), See Section VI.3., “Reporting."

3. Anticipated Announcement and Award Dates

Not Applicable.

Section VI. Award Administration Information

1. Award Notices

After the peer review of the application is completed, the PD/PI will be
able to access his or her Summary Statement (written critique) via the NIH eRA Commons.

A formal notification in the form of a Notice
of Award (NoA) will be provided to the applicant organization. The NoA
signed by the grants management officer is the authorizing document. Once all
administrative and programmatic issues have been resolved, the NoA will be
generated via email notification from the awarding component to the grantee
business official.

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Section IV.5.,
“Funding Restrictions.”

We
encourage your inquiries concerning this funding opportunity and welcome the opportunity
to answer questions from potential applicants. Inquiries may fall into three
areas: scientific/research, peer review, and financial or grants management
issues.

Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving
human subjects must be evaluated with reference to the risks to the subjects,
the adequacy of protection against these risks, the potential benefits of the
research to the subjects and others, and the importance of the knowledge gained
or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials,
including physiologic toxicity and dose-finding studies (Phase I); efficacy
studies (Phase II); efficacy, effectiveness, and comparative trials (Phase
III). Monitoring should be commensurate with risk. The establishment of data
and safety monitoring boards (DSMBs) is required for multi-site clinical trials
involving interventions that entail potential risks to the participants (NIH
Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, https://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct
costs in any single year are expected to include a plan for data sharing or
state why this is not possible (https://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions on issues related to
institutional policies and local institutional review board (IRB) rules, as
well as local, State, and Federal laws and regulations, including the Privacy
Rule. Reviewers will consider the data sharing plan but will not factor the
plan into the determination of scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to
provide access to research data through the Freedom of Information Act (FOIA)
under some circumstances. Data that are: (1) first produced in a project that
is supported in whole or in part with Federal funds; and (2) cited publicly and
officially by a Federal agency in support of an action that has the force and
effect of law (i.e., a regulation) may be accessed through FOIA. It is
important for applicants to understand the basic scope of this amendment. NIH
has provided guidance at https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include
information about this in the budget justification section of the application.
In addition, applicants should think about how to structure informed consent
statements and other human subjects procedures given the potential for wider
use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important
research resources including the sharing of model organisms for biomedical
research (see https://grants.nih.gov/grants/policy/model_organism/index.htm).
At the same time, the NIH recognizes the rights of grantees and contractors to
elect and retain title to subject inventions developed with Federal funding
pursuant to the Bayh-Dole Act (see the NIH Grants Policy Statement at https://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm).
Beginning October 1, 2004, all investigators submitting an NIH application or
contract proposal are expected to include in the application/proposal a
description of a specific plan for sharing and distributing unique model
organism research resources generated using NIH funding or state why such
sharing is restricted or not possible. This will permit other researchers to
benefit from the resources developed with public funding. The inclusion of a
model organism sharing plan is not subject to a cost threshold in any year and
is expected to be included in all applications where the development of model
organisms is anticipated.

Inclusion of Women and Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their
sub-populations must be included in all NIH-supported clinical research projects
unless a clear and compelling justification is provided indicating that
inclusion is inappropriate with respect to the health of the subjects or the
purpose of the research. This policy results from the NIH Revitalization Act of
1993 (Section 492B of Public Law 103-43). All investigators proposing clinical
research should read the "NIH Guidelines for Inclusion of Women and
Minorities as Subjects in Clinical Research (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the SF424 (R&R) application; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of
21) must be included in all clinical research, conducted or supported by the
NIH, unless there are scientific and ethical reasons not to include them.

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants
for all investigators submitting NIH applications for research involving human
subjects and individuals designated as key personnel. The policy is available
at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for Federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human Embryonic
Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility
of the applicant to provide in the project description and elsewhere in the
application as appropriate, the official NIH identifier(s) for the hESC line(s)
to be used in the proposed research. Applications that do not provide this
information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript
submission (NIHMS) system (http://www.nihms.nih.gov)
at PubMed Central (PMC) an electronic version of the author's final manuscript
upon acceptance for publication, resulting from research supported in whole or
in part with direct costs from NIH. The author's final manuscript is defined as
the final version accepted for journal publication, and includes all
modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from: 1) currently
funded NIH research projects; or 2) previously supported NIH research projects
if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award
mechanisms, cooperative agreements, contracts, Institutional and Individual
Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural
research studies. The Policy applies to peer-reviewed, original research
publications that have been supported in whole or in part with direct costs
from NIH, but it does not apply to book chapters, editorials, reviews, or
conference proceedings. Publications resulting from non-NIH-supported research
projects should not be submitted.

For more
information about the Policy or the submission process, please visit the NIH
Public Access Policy web site athttp://publicaccess.nih.gov/ and view the Policy or other Resources and Tools, including the Authors' Manual.

Standards for Privacy of Individually Identifiable Health
Information:
The Department of Health and Human Services (DHHS) issued final modification to
the "Standards for Privacy of Individually Identifiable Health Information,"
the "Privacy Rule," on August 14, 2002. The Privacy Rule is a Federal regulation under the Health Insurance Portability and Accountability Act
(HIPAA) of 1996 that governs the protection of individually identifiable health
information, and is administered and enforced by the DHHS Office for Civil
Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside
with the researcher and his/her institution. The OCR Website (http://www.hhs.gov/ocr/) provides
information on the Privacy Rule, including a complete Regulation Text and a set
of decision tools on "Am I a covered entity?" Information on the
impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within
specified page limitations. Unless otherwise specified in an NIH solicitation,
Internet addresses (URLs) should not be used to provide information necessary
to the review because reviewers are under no obligation to view the Internet
sites. Furthermore, we caution reviewers that their anonymity may be compromised
when they directly access an Internet site.

Healthy People 2010:
The U.S. Public Health Service (PHS) is committed to achieving the health
promotion and disease prevention objectives of "Healthy People 2010,"
a PHS-led national activity for setting priority areas. This PA is related to
one or more of the priority areas. Potential applicants may obtain a copy of
"Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:This program is
described in the Catalog of
Federal Domestic Assistance and is not subject to the intergovernmental
review requirements of Executive Order 12372 or Health Systems Agency review.
Awards are made under the authorization of Sections 301 and 405 of the Public
Health Service Act as amended (42 USC 241 and 284) and under Federal
Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92. All awards are subject
to the terms and conditions, cost principles, and other considerations
described in the NIH Grants
Policy Statement.

The PHS strongly encourages all grant recipients to
provide a smoke-free workplace and discourage the use of all tobacco products.
In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a facility) in
which regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent
with the PHS mission to protect and advance the physical and mental health of
the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified
health professionals who have made a commitment to pursue a research career
involving clinical, pediatric, contraception, infertility, and health
disparities related areas. The LRP is an important component of NIH's efforts
to recruit and retain the next generation of researchers by providing the means
for developing a research career unfettered by the burden of student loan debt.
Note that an NIH grant is not required for eligibility and concurrent career
award and LRP applications are encouraged. The periods of career award and LRP
award may overlap providing the LRP recipient with the required commitment of
time and effort, as LRP awardees must commit at least 50% of their time (at
least 20 hours per week based on a 40 hour week) for 2 years to the research.
For further information, please see http://www.lrp.nih.gov.